Genetic instability in radiation-induced leukaemias: mouse models.

PURPOSE: Genetic instability plays a major role in multi-stage carcinogenesis. Ionizing radiation induces delayed genetic instability which can be transmitted to the clonal offspring of the irradiated cell, so it is of considerable importance to determine whether radiation-induced genetic instability contributes to radiation-leukaemogenesis. RESULTS: The experimental data obtained using radiation-induced leukaemias in mouse models were reviewed, and an attempt was made to distinguish between the instability detectable in de novo cancers and that which is associated with ionising radiation. Genetic lesions identified in mouse leukaemias include non-clonal chromosomal aberrations, loss of heterozygosity, and minisatellite/microsatellite mutations. CONCLUSIONS: Studies of mouse radiation-induced leukaemias have detected evidence of genetic instability. However, with few exceptions, most of this instability was also observed during de novo multi-stage carcinogenesis. This raises the possibility that radiation induces ongoing genetic instability that is functionally indistinguishable to that implicated in de novo tumour progression.